Can adipokines serum levels be used as biomarkers of hand osteoarthritis?

PURPOSE: To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). METHODS: 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren-Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. RESULTS: Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. CONCLUSIONS: This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.

Ultrasound detected inflammation is associated with the development of new bone erosions in hand osteoarthritis: a longitudinal study over 3.9 years.

OBJECTIVE: To evaluate the association between ultrasound (US) detected inflammation at baseline and the subsequent development of new bone erosions at follow-up in patients with hand osteoarthritis (HOA). METHOD: 32 of the 35 (10 controls, 12 patients with non erosive HOA (non-EHOA), 13 with EHOA subjects originally studied were re-evaluated 3.9 years after the initial study, by means of standard radiography and US examination. Kellgren-Lawrence (K-L) and Kallman scores were utilized to evaluate 576 interphalangeal (IP) joints. US detected synovial inflammation features were scored as present/absent. US detected bone erosions were also investigated. The association between synovial inflammation features at baseline and the development of new bone erosions was evaluated using the generalized linear mixed model (GLMM) after adjustment for patient effect, age, gender, body mass index. RESULTS: In HOA patients, radiographic scores worsened and bone erosions progressed. In HOA patients similar percentages of joints with Power Doppler Signal (PDS) and gray scale (GS) synovitis were found comparing baseline and follow-up examinations, whilst a significant increase was found in the joints with effusions. Only a minority of joints were positive on both occasions (between 2 and 6 %), the majority fluctuated between positive and negative and vice versa. PDS positivity was associated with new radiographic central erosions and US-detected bone erosions, whereas GS synovitis and effusion were not. CONCLUSIONS: Radiographic scores and bone erosions increased over a period of about 4 years. Synovial inflammation as detected by PDS was associated with the appearance of new bone erosions.

Cognitive impairment is a negative short-term and long-term prognostic factor in elderly patients with hip fracture.

BACKGROUND: Subjects with severe cognitive impairment (CI) have a high-risk of hip fractures with increased rate of adverse postoperative functional outcomes and mortality. AIM: To evaluate the impact of different degrees of CI on functional recovery and mortality after hip fracture. DESIGN: Prospective observational study. SETTING: Two orthopedic surgery units. POPULATION: Two hundred twenty-eight consecutive patients after a hip surgery. METHODS: Patients were assessed at baseline through the Short Portable Mental Status Questionnaire (SPMSQ), an instrument that allows to categorize subjects as follows: cognitively intact (SPMSQ≥8) or with mild (SPMSQ=6-7), moderate (SPMSQ=3-5) and severe CI (SPMSQ<3). Barthel Index (BI) was used to assess functional disability. All patients underwent rehabilitation from the day after surgery to discharge (mean length of stay =10.2±3.4). Outcome measures were: (1) overall mortality up to 12 months after surgery; (2) motor ability achieved at discharge from the orthopedic ward (sitting, standing, walking); (3) BI and SPMSQ at 1, 3, 6 and 12 months postoperatively. RESULTS: All degrees of severity of CI were inversely correlated to the ability to walk at hospital discharge. At one year from surgery, the majority of patients with CI were functionally severely dependent, whereas about half of the cognitively intact ones gained a functional independence status. CI and the level of premorbid disability influenced the risk of death. CONCLUSION: CI for all degrees of severity is a negative prognostic factor in elderly patients with hip fracture. CLINICAL REHABILITATION IMPACT: We suggest evaluating the cognitive status of patients with hip fracture as it affects both the short and long-term functional recovery at any degree of severity.

Clinical associations in patients with hand osteoarthritis.

OBJECTIVES: To investigate the clinical associations of hand osteoarthritis (HOA) and their relationships with radiographic features. METHODS: A total of 446 patients with hand osteoarthritis (HOA; 233 with erosive HOA (EHOA) and 213 with non-EHOA) and 307 controls were evaluated. Demographic and clinical data from patients and controls were recorded based on medical records/clinical reports and an anamnesis of drug consumption. Posteroanterior radiographs of both hands were obtained from all HOA patients and were assessed using the Kellgren and Lawrence (K&L) and Kallman scoring systems. RESULTS: After adjustment for age, gender, and body mass index (BMI), HOA patients showed a significantly increased odds ratio (OR) for hypercholesterolaemia [OR 2.10, 95% confidence interval (CI) 1.39-3.16, p < 0.0005] and autoimmune thyroiditis (OR 4.85, 95% CI 1.77-13.29, p = 0.002), as well as for knee (OR 1.63, 95% CI 1.09-2.44, p = 0.018) and hip OA (OR 1.87, 95% CI 1.07-3.27, p = 0.029). No significant increase for systemic hypertension, ischaemic heart disease, and diabetes mellitus was found. Patients with EHOA and non-EHOA showed similar risks for the above-mentioned co-morbidities. A similar occurrence of clinical associations was also observed in patients with HOA alone and in those with generalized OA. No association between radiographic scores and clinical associations was observed. CONCLUSIONS: Patients with HOA present a direct association with hypercholesterolaemia (and autoimmune thyroiditis) but do not show increased ischaemic cardiovascular manifestations compared to controls. No significant association between radiographic scores and co-morbidities was found.

Prediction of incident hip fracture by femoral neck bone mineral density and neck-shaft angle: a 5-year longitudinal study in post-menopausal females.

OBJECTIVE: To compare hip fracture incidence in post-menopausal females who were differently stratified for the fracture risk according to bone mineral density and proximal femur geometry. METHODS: In a 5 year follow-up study, the hip fracture incidence in 729 post-menopausal females (45 of whom suffered from incident hip fracture) was assessed and compared. Forward logistic regression was used to select independent predictors of hip fracture risk, including age, age at menopause, height, weight, femoral neck bone mineral density (FNBMD), neck-shaft angle (NSA), hip axis length, femoral neck diameter and femoral shaft diameter as covariates. Fracture incidence was then calculated for the categories of young/old age, high/low FNBMD and wide/narrow NSA, which were obtained by dichotomising each hip fracture independent predictor at the value best separating females with and without a hip fracture. RESULTS: The hip fracture incidence of the whole cohort was significantly higher in females with a wide NSA (8.52%) than in those with a narrow NSA (3.51%). The combination of wide NSA and low FNBMD had the highest hip fracture incidence in the whole cohort (17.61%) and each age category. The combinations of narrow/wide NSA with low/high FNBMD, respectively, gave a significantly higher fracture incidence in older than in younger women, whereas women with a combined wide NSA and low FNBMD had no significantly different fracture incidence in young (14.60%) or old age (21.62%). CONCLUSION: Our study showed that NSA is effective at predicting the hip fracture risk and that the detection in early post-menopause of a wide NSA together with a low FNBMD should identify females at high probability of incident hip fracture.

Ultrasound-detected synovitis with power Doppler signal is associated with severe radiographic damage and reduced cartilage thickness in hand osteoarthritis.

OBJECTIVES: To examine ultrasound (US) features of synovitis in hand osteoarthritis (OA) joints, and to evaluate their relationship with radiological damage severity and US-detected cartilage thickness. METHODS: US examination was carried out on 14 joints of both hands of 25 patients with symptomatic hand OA (HOA) and 10 age- and sex-matched control subjects. US-detected features were: synovial hypertrophy, effusion, power Doppler signal (PDS), cartilage thickness. Conventional hand radiographs were scored utilizing the Kellgren-Lawrence and Kallman systems. HOA patients were divided into two subsets: non-erosive and erosive. RESULTS: Among the three groups of subjects studied, erosive OA showed the highest values of radiological scores and the highest prevalence of US-detected synovitis. Joints positive for US synovitis features (above all PDS) had higher radiological scores and lower cartilage thickness, while joints with X-ray detected central erosions [the hallmark of erosive HOA were more likely to present PDS positivity. US measured cartilage thickness inversely correlated with radiological damage scores. CONCLUSIONS: US-detected synovitis is present in about 10% of HOA finger joints and is associated with more severe radiological damage and reduced cartilage thickness. PDS and cartilage thickness (mm) may represent two innovative additional information tools provided by ultrasonography in HOA evaluation.

Survival in high-grade osteosarcoma: improvement over 21 years at a single institution.

BACKGROUND: The purpose of this study was to analyze improvements in overall survival over 21 years (1982-2002), with a 5-year minimum follow-up, in the largest series from a single center ever reported. MATERIALS AND METHODS: All diagnoses of high-grade osteosarcoma were included despite histological varieties, age, site and stage. Of the 1656 cases observed, 198 patients were excluded (41 consultation only, 129 low-grade varieties, and 28 lost to follow-up). Within 1458 included patients, 1032 had characteristics to be enrolled in conventional clinical trials (classic histology, age <41, localized, and extremity disease). Data are also analyzed in subgroups to define patients who benefited most. RESULTS: With a median follow-up of 12 years (5-25 years), 754 patients (51.7%) are alive, of whom 613 continuously disease free. Survival at 5, 10, and 15 years is 57%, 52%, and 51%, respectively. Patients candidates for clinical trials have a survival rate of 68%, 64%, and 61%, respectively. Survival for the other patients is 30%, 25%, and 24%, respectively. Trend (joinpoint statistical analysis at real 5-year follow-up) shows a yearly statistically significant improvement of 1.31% (95% confidence interval 0.5% to 2.1%) from 51% for patients treated in 1982 to 68% for those treated in 2002. Patients who statistically benefited were those who relapsed or presented with metastatic disease at diagnosis or had axial tumors. CONCLUSIONS: Despite the lack of new drugs for osteosarcoma, survival has statistically improved, especially for those patients with the worst outcome. Aggressive treatments are recommended for all patients including those with poor prognosis.

Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients.

One-day surgery for acquired forefoot deformity: sciatic nerve blockade with mepivacaine vs mepivacaine+ropivacaine: a prospective, randomized study.

AIM: The aim of the study was to determine the doses of ropivacaine combined with mepivacaine for sciatic nerve blockade to enable the extension of analgesia without prolonged motor blockade, for the management of very painful operations in one-day surgery. METHODS: After obtaining approval by the ethics committee and written informed consent, we recruited 30 ASA I-III patients undergoing corrective orthopedic surgery of the forefoot in one-day surgery with sciatic nerve blockade. The patients were randomly divided into 3 groups: one control group, treated by 1.5% mepivacaine (300 mg), and two groups differentiated by the dose of 0.5% ropivacaine (25 and 40 mg) used in combination with 1.5% mepivacaine (225 mg). The offset data of the blockade were obtained by a self-assessment form filled in by the patients, and a direct check on discharge by a blinded observer. RESULTS: There was no significant difference in the duration of the blockade among the 3 groups; the extension of analgesia was significant (P<0.003) in the group treated by mepivacaine+ropivacaine 40 mg (mean 477+/-255 min). CONCLUSION: Adequate doses of ropivacaine added to mepivacaine for peripheral blockade produce and increase the duration of analgesia without influencing the criteria for discharge after Day Surgery.

Long-term outcome for patients with non-metastatic Ewing's sarcoma treated with adjuvant and neoadjuvant chemotherapies. 402 patients treated at Rizzoli between 1972 and 1992.

We evaluated the long-term results obtained in 402 patients with non-metastatic Ewing's sarcoma (ES) of the bone treated in a single institution with adjuvant and neoadjuvant chemotherapies between 1972 and 1992. Multivariate analyses showed male gender, age older than 14 years, high serum lactate dehydrogenase (LDH) level, axial location of the tumour, use of radiotherapy alone as a local treatment, and poor histological response to chemotherapy, to be independent, adverse prognostic factors for event-free survival (EFS). At a mean follow-up of about 18 years (10-30 years), 177 patients (44.0%) remained continuously free of disease, 2 died of doxorubicin-induced cardiotoxicity and 8 developed a second neoplasm (5 died, and 3 are alive and free of disease). 215 patients relapsed with metastases and/or local recurrence: 14 are alive and free of disease, 1 is alive with uncontrolled disease, and 200 died. The overall survival (OS) at real follow-ups of 5-, 10-, 15- and 20-years was 57.2, 49.3, 44.9 and 38.4%, respectively. We conclude that since local or systemic relapses, treatment-complications and second malignancies are more common after 5 years or more from the beginning of treatment; a long-term follow-up is mandatory for patients with ES.

Twenty-year follow-up of osteosarcoma of the extremity treated with adjuvant chemotherapy.

We have updated the results of an adjuvant chemotherapy study of 106 patients with osteosarcoma of the extremities published 17 years ago, treated by surgery followed by adjuvant chemotherapy with vincristine (VCR), methotrexate (MTX) and doxorubicin (ADM), between 1980-1983, and followed-up for at least 20 years (20-23 years). In comparison with the results reported 17 years ago with a median follow-up of 38 months (range: 27-66), this updated study showed 24 more deaths, 9 more relapses and 3 second malignancies. Consequently, event-free survival (EFS) and overall survival (OS) are significantly lower compared to the previous study with a 3-year follow up (EFS 38% vs 53%; OS 43.8% vs 67%). We conclude that osteosarcoma patients treated with chemotherapy are at risk of late adverse events. Protracted medical follow-up and long-term updated results are useful to identify, at an early stage, late relapses and late treatment-related complications.

Neoadjuvant chemotherapy for Ewing's tumour of bone: recent experience at the Rizzoli Orthopaedic Institute.

The results achieved in 157 patients with non-metastatic Ewing's sarcoma of the bone treated at a single institution between 1991 and 1997 according to a new protocol (REN-3) are reported. Induction chemotherapy consisted of two cycles of 'VAC': vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of 'VIAc': V, ifosfamide (I), actinomycin (Ac). After local treatment, patients received three more cycles of VAC, two of VIAc, three cycles of I plus etoposide (E) and two cycles with V, C and Ac. Local treatment was surgery in 53% of patients, surgery+radiotherapy in 25% and radiotherapy only in 22%. With a follow-up ranging between 4 and 10 years (mean: 7 years), 110 patients (70%) remained continuously event-free, 2 patients died of toxicity and 45 patients relapsed: 33 due to metastases and 12 due to local recurrence always associated with metastases. The 5-year event-free survival (EFS) and overall survival (OS) were 71.0 and 76.5% respectively. These results are significantly better that the ones achieved in our previous three studies in which a three-drug VAC regimen (REA-1), and 4-drug VACAc regimen (REA-2 and REN-1) was used, and in our most recent study (REN-2) which was based on a six-drug regimen as in the present study, but where I and Ac were used only after the local treatment. However, since REN-3 surgery was used in a significantly larger number of patients, we cannot say whether the better outcome of this study was due to the use of a six-drug regimen with an early delivery of ifosfamide and actinomycin, or to the wider use of surgery as local treatment or both.

Pulsed venous flow pattern with hemodilution.

Venous flow pattern changes and venous flow were assessed in relation to the degree of hemodilution. Femoral vein flow was measured with a duplex scanner in two groups of 11 patients 20 days and 5 days preoperatively, and 1 day postoperatively. In group I, hemodilution was used and patients gave three autologous blood predonations between day 20 and day 5. Perioperative blood loss was reintegrated by electrolyte solution. In group II, hemodilution was not used and autologous blood predonations were not carried out. These patients received a perioperative homologous blood transfusion of 800 mL. Hemoglobin was lower on day 5 (11.3 +/-1.4 vs 13.1 +/-1 g/dL, p<0.05) and on postoperative day 1 (8.9 +/-1.6 vs 10.6 +/-1, p<0.05) in group I. The decrease in hemoglobin was associated with an increase in blood flow and a pulsed venous flow pattern in 14 of 22 veins after autologous blood predonation and in 21 of 22 veins on postoperative day 1 (p<0.05). Increased venous flow in hemodilution is associated with a pulsed venous flow pattern.

[Orthopaedic one day surgery: anaesthesiologic techniques used and intra- and postoperative complications]. / One day surgery otropedico: tecniche anestesiologiche utilizzate e complicanze intra- e postoperatorie.

OBJECTIVE: Optimize patient management in one day surgery (ODS) by an observative study regarding one day orthopaedic surgery, assessing kind and quantity of intra- and postoperative complications, need for prolonged postoperative assistance postponing discharge, recovery in other hospitals, patients satisfaction index. METHODS: From september 1999 until december 2000 we distributed a questionnaire 1286 consecutive patients. The patients were ASA I (80,7%), ASA II (17%) and ASA III (2,3%). We evaluated intra- and postoperative complications considering type of surgery and anaesthesiologic technique; need and reason for medical consulting; if consulting took place in other institutes. Patients judgement regarding medical and nursing assistance during in hospital stay was assessed. RESULTS: Main surgical procedures: arthroscopy (44,6%), internal fixation removal (21,3%), neurolysis (9,5%), cysts/tumours/nodules removal (7,5%), foot surgery (8,0%). Used anaesthesiologic techniques: neural block (65,6%), plexus block (15,1%), general (12,5%), spinal (4,8%) and local anaesthesia (1,9%). An intraoperative complication (convulsion) was reported twice. Postoperative complications: pain (3,6%) most frequent in foot surgery (5,2%), nausea (0,2%), fever (0,7%), haematoma (0,5%). 5 delayed discharges (beyond 24h) were reported, for surgical reasons. In 5 cases another institute was visited. There were no deads. CONCLUSIONS: The percentage of not planned recoveries (0,1%) is an indication of frequency of major complications. Satisfaction index of patients was high (96%). Kind of surgical procedure and anaesthesiologic technique, considering the minimal intra- and postoperative complications, are adjusted to the ODS regime. Reinforcing analgesic protocols in foot surgery though are necessary. According to our opinion the peripheral block is preferable in orthopaedic ODS.

Effects of predeposit and intentional perioperative haemodilution on blood saving program in major orthopaedic surgery.

In this study we evaluated the effects of predeposit and intentional perioperative haemodilution on a blood saving program in major orthopaedic surgery. We demonstrated that autologous blood phlebotomy and maintenance of optimal levels of perioperative haemodilution by delaying blood transfusion, even autologous, are efficient techniques in reducing homologous, red blood cell (HRBC) transfusion. Patients who received autologous red blood cell (ARBC) or HRBC more than one day after surgery, while having Hb values <8 g/dl, are less at risk of needing the first or additional HRBCs. In conclusion, predeposit and intentional haemodilution obtained by delaying blood transfusions, even autotransfusional, is a correct way of conducting a blood saving program (BSP) in major orthopaedic surgery. These techniques are clinically effective in avoiding or reducing HRBC transfusion.

Thromboembolic complications and pharmacological prophylaxis in orthopaedic surgery.

Two thousand, three hundred and three patients who had undergone major orthopaedic surgery were statistically analysed for the incidence of complications comparing three regimens of prophylaxis and coexisting diseases; 2090 patients did not present postoperative complications. PTE occurred in 0.65% (one fatal). The mortality rate was 0.34% and the incidence of haemorrhage (haematoma and one gastric haemorrhage) was 3.8%. Patients treated with indobufen had a shorter hospital stay and the need for homologous blood transfusions was lower than for patients treated with calcium heparin. The rate of PTE was notably different in the three groups, being lower in the group treated with enoxaparin, although this result was not found to be statistically significant.

Data management in gait analysis for clinical applications.

OBJECTIVE: To study the reliability of gait analysis data obtained using the Calibrated Anatomical System Technique (CAST) protocol and to verify the suitability and repeatability of the extraction of a number of parameters from the waveforms obtained. DESIGN: The experimental protocol and the parametric analysis technique were applied on a population of able-bodied subjects. BACKGROUND: The clinical interpretation process of gait data still needs a more accurate analysis of the reliability and repeatability of the measurements and a suitable procedure for data reduction useful for data comparison. METHODS: Gait analysis was performed in 20 able-bodied subjects using a stereophotogrammetric system and a forceplate. 124 parameters relative to time-distance, kinematic and kinetic variables were calculated by means of an automatic procedure and statistically analysed. RESULTS: Most of the parameters were found to be normally distributed with relatively small range of variation. Few of them showed poor repeatability, mostly due to the experimental inaccuracies introduced. Correlation of several gait parameters with age, sex, and speed of progression was also identified.